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Biomedical subjects

A D Russell

Publications and source records attributed to A D Russell.

At least 19 recordsLinked to original sources
PubMed2005

A strategy for the control of catheter blockage by crystalline Proteus mirabilis biofilm using the antibacterial agent triclosan.

OBJECTIVES: Catheter blockage by crystalline Proteus mirabilis biofilm is a common complication in patients undergoing long-term indwelling bladder catheterisation. Previously we have shown that inflating the retention balloons of all-silicone catheters with triclosan solutions prevents the encrustation process. The aim of the present work was to examine whether this strategy is effective in latex-based catheters. METHODS: Laboratory bladder models were fitted with catheters and the retention balloons inflated with water or various concentrations of triclosan. The urine was inoculated with Pr. mirabilis and the times catheters took to block recorded. RESULTS: Control catheters blocked in mean times ranging from 18 to 27 h. The pH of the urine rose from 6.1 to >8.6. In models with latex-based catheters inflated with 1-10 mg/ml triclosan, the urinary pH was controlled, the numbers of organisms in the urine was reduced and the catheters drained freely for the 7 day experimental period. Electron microscopy confirmed that crystalline biofilm was blocking control catheters. Little sign of encrustation was visible on the test catheters. CONCLUSION: Inflating the retention balloons with triclosan could have practical applications in controlling encrustation on both latex and silicone-based catheters.

Anti-Bacterial Agents↗
PubMed2005

Antimicrobial activity of chlorhexidine diacetate and benzalkonium chloride against Pseudomonas aeruginosa and its response to biocide residues.

AIMS: The aims of this study were to evaluate the antimicrobial activity of chlorhexidine diacetate (CHX) and benzalkonium chloride (BZK) for strains of Pseudomonas aeruginosa exhibiting increased minimum inhibitory concentrations (MIC) for CHX, and to determine whether residues of chlorhexidine digluconate (CHG) and Hibiscrub (Hib, a formulation containing CHG) affect the susceptibility of P. aeruginosa to these biocides and a number of antibiotics. METHODS AND RESULTS: The bactericidal activity of CHX and BZK was evaluated for strains of P. aeruginosa exhibiting increased MIC for CHX with established suspension and surface disinfection tests. None of the strains of P. aeruginosa exhibiting raised MIC for CHX was less sensitive than the parent strain to CHX or BZK in either method. A test was designed to investigate the effects of dried CHG and Hib residues on P. aeruginosa cells. Exposure of P. aeruginosa to dried residues of CHG or Hib did not result in the organism becoming less sensitive to either biocide or a number of antibiotics. CONCLUSIONS: Pseudomonas aeruginosa strains with raised MIC to CHX were no less sensitive than the parent strain to CHX and BZK in bactericidal investigations. Exposure to dried residues of CHG and Hib did not render P. aeruginosa less sensitive to either of these agents or a number of antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: An increase in the MIC for a biocide in a micro-organism does not necessarily result in a failure of the biocide to effectively kill the organism. The residue that remains after the use of an antimicrobial agent can be at a far lower concentration than that initially applied and this study highlights the necessity for further investigations into the effect of residues, at low concentration, on bacterial populations and their role, if any, in the continued problem of antibiotic resistance.

Anti-Bacterial Agents↗
PubMed2005

Triclosan-bacteria interactions: single or multiple target sites?

AIMS: To investigate the inhibitory and lethal effects of triclosan against several micro-organisms at different stages of their phase of population growth. METHODS AND RESULTS: Triclosan minimum inhibitory concentrations against several test organisms were determined in broth and agar using standard protocols. The bisphenol effect on bacterial population growth kinetics was studied using the Bioscreen C microbial growth analyser. Finally, the efficacy of triclosan on phases of bacterial growth was determined using a standard suspension test. The duration of the lag phase for all micro-organisms tested was increased by bisphenol in a concentration-dependent manner. The population growth kinetics of the micro-organisms was also altered after biocide exposure. At higher concentrations, triclosan was bactericidal regardless of their phase of population growth, although population in stationary phase and particularly, washed suspensions, were more resilient to the lethality of triclosan. This lethal activity was concentration and contact time dependent, and in some instances, bactericidal activity of bisphenol was observed within 15 s. CONCLUSIONS: Low concentrations of triclosan affected the growth of several bacteria, while higher concentrations were bactericidal regardless of the bacterial phase of population growth. SIGNIFICANCE AND IMPACT OF THE STUDY: Here, we presented clear evidence that the interaction of triclosan with the bacterial cell is complex and its lethality cannot be explained solely by the inhibition of metabolic pathways such as the enoyl acyl-reductase. However, the inhibition of such pathways cannot be ruled out as part of the lethal mechanism of the bisphenol at a low bactericidal concentration.

Anti-Infective Agents, Local↗
PubMed2004

BMS-201620: a selective beta 3 agonist.

A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human beta3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent beta3 full agonist (Ki = 93 nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation.

Adrenergic beta-3 Receptor Agonists↗
PubMed2004

Whither triclosan?

Triclosan has activity against many, but not all, types of Gram-positive and Gram-negative bacteria. It is bacteriostatic at low concentrations, but higher concentrations are bactericidal. Pseudomonas aeruginosa is highly resistant, whereas methicillin-resistant Staphylococcus aureus strains are inhibited over a range of approximately 0.1-2 mg/L. Triclosan shows significant activity against some mycobacteria, but is not sporicidal. Its growth-inhibitory properties result from an inhibition of enoyl reductase, FabI. Membrane-destabilizing effects are likely to be responsible for bacterial inactivation by higher concentrations. Resistance can arise from mutations in, and/or overproduction of, FabI, impermeability or efflux. Whilst triclosan resistance in laboratory experiments may be associated with changes in antibiotic susceptibility, comprehensive environmental surveys have not demonstrated any association between triclosan usage and antibiotic resistance. Triclosan has several important uses, and the future aim must be to retain these applications whilst eliminating the more frivolous and unnecessary ones.

Anti-Infective Agents, Local↗
PubMed2004

Resistance, biguanide sorption and biguanide-induced pentose leakage during encystment of Acanthamoeba castellanii.

AIMS: This study investigates the effects of biguanides during encystment of Acanthamoeba castellanii. METHODS AND RESULTS: A non-nutrient encystment system was used to investigate the changes in the levels of sorption (uptake) of three non-cysticidal concentrations (10, 20 and 50 microg ml(-1)) of chlorhexidine diacetate (CHA) and polyhexamethylene biguanide (PHMB) as well as their effects on viability and leakage of pentose sugars during the first 36 h of encystment. Trophozoites treated with CHA or PHMB were more sensitive and generally sorbed more of each biocide than cysts. During encystment, the largest increases in resistance developed between 18 and 36 h for both biguanides with the resistance emerging to biguanide concentrations of 10 or 20 microg ml(-1) between 18 and 24 h. At 50 microg ml(-1) resistance emerged between 24 and 36 h. There was a general decrease in biocide sorption during encystment between 0-24 and 0-21 h for CHA and PHMB, respectively, at a concentration of 50 microg ml(-1). The greatest decline in biguanide-induced pentose leakage was between 0 and 12 h. CONCLUSIONS: The results suggest that during encystment some of the changes in the susceptibility to CHA or PHMB may be related to decreases in the levels of biocide sorption, which is limited by the developing cyst wall. SIGNIFICANCE AND IMPACT OF THE STUDY: During encystation, changes occur in biguanide sensitivity. The physical barrier of the cyst wall may be an important factor in limiting biocide sorption.

Acanthamoeba↗
PubMed2003

Similarities and differences in the responses of microorganisms to biocides.

Unlike antibiotics, biocides are multi-targeted antimicrobial agents. Several of the damaging effects reported to occur in the most widely studied organisms, bacteria, may also take place to varying degrees in other organisms. Nevertheless, there is considerable variation in the response of different microorganisms to biocides. Bacteria themselves (Gram-positive and Gram-negative vegetative organisms, mycobacteria and spores) respond differently to biocides and this disparity is widened when yeasts, moulds, protozoa and algae are considered. The underlying reasons for these varied responses are poorly understood at present, but the chemical composition of outer cellular layers is likely to be a factor of prime importance. Other possible contributory factors may be differences in stress responses, the presence of efflux pumps and cells occurring within biofilms or algal mats.

Animals↗
PubMed2003

Control of encrustation and blockage of Foley catheters.

Urinary catheters often become encrusted and blocked by crystalline Proteus mirabilis biofilms. Results of experiments in a laboratory model of a Foley catheterised bladder infected with P mirabilis showed that when retention balloons were inflated with a solution of triclosan (10 g/L), the catheters drained freely for at least 7 days. Triclosan became impregnated throughout the silicone catheter material and completely inhibited the formation of crystalline biofilm, whereas catheters inflated with water became blocked in 24 h. Our observations suggest a way to control a common complication in patients with long-term indwelling bladder catheters.

Biofilms↗
PubMed2003

Development of bacterial resistance to several biocides and effects on antibiotic susceptibility.

The aims of this study were to investigate the development of bacterial resistance to eugenol, thymol, trichlorocarbanalide (TCC), didecyldimethylammonium chloride (DDDMAC) and C10-16-alkyldimethyl, N-oxides (ADMAO) and subsequent effects on antibiotic susceptibility. An agar minimum inhibitory concentration (MIC) method was used to assess the activity of the biocides against standard bacterial strains and laboratory mutants. A range of techniques including disk diffusion and gradient plate experiments were used to attempt to develop bacterial 'resistance' or tolerance to the biocides. The mutants produced were examined for cross-resistance to the other biocides and to antibiotics via disk diffusion and gradient plate MIC methods. Outer membrane proteins of the mutants were extracted and examined using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Escherichia coli triclosan-resistant mutants were not cross-resistant to eugenol, thymol, TCC, DDDMAC and ADMAO. Mutants with elevated MICs to DDDMAC (E. coli and Pseudomonas aeruginosa), thymol (E. coli) and eugenol (E. coli) were isolated, but all remained sensitive to higher concentrations of the agents. Bacteria with elevated MICs to TCC and ADMAO were not obtained. Some low-level cross-resistance between DDDMAC, eugenol and thymol was observed with the E. coli gradient plate mutants, as well as reduced susceptibility to antibiotics, most notably chloramphenicol. The lack of cross-resistance of the triclosan mutants suggested that the mode of action of triclosan is not shared with the other biocides studied. SDS-PAGE results indicated that the DDDMAC P. aeruginosa mutant had a reduced amount (or absence) of one outer membrane protein in comparison with the standard strain. In conclusion, under laboratory conditions, bacterial exposure to thymol, eugenol and DDDMAC can lead to reduced susceptibility between selected biocidal agents and antibiotics, more specifically, chloramphenicol. However, further studies are required to determine if this is of clinical significance.

Anti-Infective Agents, Local↗
PubMed2003

Biocide use and antibiotic resistance: the relevance of laboratory findings to clinical and environmental situations.

Antibiotics are used as chemotherapeutic drugs, and biocides are used as antiseptics, disinfectants, and preservatives. Several factors affect biocidal activity, notably concentration, period of contact, pH, temperature, the presence of interfering material, and the types, numbers, location, and condition of microorganisms. Bacterial cells as part of natural or artificial (laboratory) biofilm communities are much less susceptible than planktonic cells to antibiotics and biocides. Assessment of biocidal activity by bactericidal testing is more relevant than by determination of minimum inhibitory concentrations. Biocides and antibiotics may show some similarities in their mechanisms of action and common mechanisms of bacterial insusceptibility may apply, but there are also major differences. In the laboratory, bacteria can become less susceptible to some biocides. Decreased resistance may be stable or unstable and may be accompanied by a low-level increase in antibiotic resistance. Laboratory studies are useful for examining stress responses and basic mechanisms of action and of bacterial insusceptibility to antibacterial agents. Translation of such findings to the clinical and environmental situations to provide evidence of a possible relation between biocide use and clinical antibiotic resistance is difficult and should be viewed with caution.

Anti-Bacterial Agents↗
PubMed2003

Activity and mechanisms of action of selected biocidal agents on Gram-positive and -negative bacteria.

AIMS: This study investigates the antimicrobial activity and mode of action of two natural products, eugenol and thymol, a commonly utilized biostatic agent, triclocarban (TCC), and two surfactants, didecyldimethylammonium chloride (DDDMAC) and C10-C16 alkyldimethyl amine N-oxides (ADMAO). METHODS AND RESULTS: Methods used included: determination of minimum inhibitory concentrations (MICs), lethal effect studies with suspension tests and the investigation of sub-MIC concentrations on growth of E. coli, Staph. aureus and Ps. aeruginosa using a Bioscreen microbiological analyser. Leakage of intracellular constituents and the effects of potentiating agents were also investigated. Only DDDMAC was bactericidal against all of the organisms tested. Eugenol, thymol and ADMAO showed bacteriostatic and bactericidal activity, but not against Ps. aeruginosa. TCC was only bacteristatic against Staph. aureus, but like the other agents, it did affect the growth of the other organisms in the Bioscreen experiments. All of the antimicrobial agents tested were potentiated by the permeabilizers to some extent and leakage of potassium was seen with all of the agents except TCC. CONCLUSIONS: DDDMAC was bactericidal against all organisms tested and all compounds had some bacteriostatic action. Low level static effects on bacterial growth were seen with sub-MIC concentrations. Membrane damage may account for at least part of the mode of action of thymol, eugenol, DDDMAC and ADMAO. SIGNIFICANCE AND IMPACT OF THE STUDY: The ingredients evaluated demonstrated a range of bactericidal and bacteriostatic properties against the Gram-negative and -positive organisms evaluated and the membrane (leakage of intracellular components) was implicated in the mode of action for most (except TCC). Sub-MIC levels of all ingredients did induce subtle effects on the organisms which impacted bacterial growth, even for those which had no true inhibitory effects.

Anti-Bacterial Agents↗
PubMed2003

Effects of ortho-phthalaldehyde, glutaraldehyde and chlorhexidine diacetate on Mycobacterium chelonae and Mycobacterium abscessus strains with modified permeability.

The mechanisms of the mycobactericidal action of ortho-phthalaldehyde (OPA), glutaraldehyde (GTA) and chlorhexidine diacetate (CHA) were investigated using mycobacterial spheroplasts of two reference strains, Mycobacterium chelonae NCTC 946, Mycobacterium abscessus NCTC 10882 and two GTA-resistant strains, M. chelonae Epping and M. chelonae Harefield. Transmission electron microscopy of the spheroplasts revealed an altered cell wall structure compared with the parent cells. Structural alterations resulting from the spheroplasting process were in part correlated to a loss of lipid content. Low concentrations of CHA induced protein coagulation in M. chelonae NCTC 946 spheroplasts, which also exhibited the highest loss of free non-polar lipids. Higher concentrations of CHA were required to produce similar results to the other spheroplasts investigated in which there was a less substantial decrease in lipid content. OPA (0.5% w/v) readily penetrated the residual cell wall and cytoplasmic membrane, producing significant protein coagulation in M. chelonae NCTC 946. GTA (0.5% v/v) induced a similar effect but to a lesser extent. Pre-treatment of the spheroplasts with OPA and GTA and their subsequent suspension in water demonstrated that GTA was a more potent cross-linking agent. This protective effect of GTA results from extensive cross-linking of amino and/or sulphydryl side-chain groups of proteins. The rapid mycobactericidal effect of OPA probably arises from its more efficient penetration across biological membranes. Mycobacterial spheroplasts represented a useful cellular model with an altered cell wall permeability. This study also showed the importance of the mycobacterial cell wall in conferring intrinsic resistance to CHA.

Cell Wall↗
PubMed2003

Bacterial outer membrane and cell wall penetration and cell destruction by polluting chemical agents and physical conditions.

In the environment, bacteria and other microorganisms are subjected to a variety of constantly changing chemical and physical agencies. Chemical ones include antimicrobial compounds (both biocides and antibiotics), pollutants, drugs, cosmetic and pharmaceutical ingredients and pesticides. The physical agents include desiccation and drying, osmotic pressure, hydrostatic pressure, temperature and pH changes and radiations (ultraviolet, sunlight, ionizing). Bacteria must thus adapt to survive these inimicable conditions. Organisms such as bacterial spores usually survive, whereas other types of microorganisms may be much more susceptible. Depending on the type of organism, the bacterial cell wall, outer membrane or the spore outer layers may act as permeability barriers to the intracellular uptake of antibiotics and biocides. Some antibacterial agents interact with, and damage or modify, the outer components. Physical agencies are known to damage the cytoplasmic membrane or to produce alterations in DNA or proteins or enzymes. Nevertheless, significant damage to the cell wall or outer membrane may also occur. Four types of organisms are considered: cocci, mycobactria, Gram-negative bacteria and bacterial spores. The nature of the damage inflicted on, or in some cases prevented by, their outer cell layers is discussed for each type of organism.

Anti-Bacterial Agents↗
PubMed2003

Lethal effects of heat on bacterial physiology and structure.

High temperatures have profound effects on the structural and physiological properties of sporulating and non-sporulating bacteria, with membranes, RNA, DNA, ribosomes, protein and enzymes all affected. Nevertheless, it is apparent that no one single event is responsible for cell death. The induction of intracellular heat-shock proteins and the activation of extracellular alarmones in vegetative cells exposed to mildly lethal temperatures are important cell responses. In bacterial spores, several factors contribute to the overall resistance to moist (wet) and dry heat; the latter, but not the former, induces mutations. Heat resistance develops during sporulation, when spore-specific heat-shock proteins are also produced. Heat sensitivity is regained during germination of spores.

Adaptation, Physiological↗
PubMed2002

Chloroxylenol- and triclosan-tolerant bacteria from industrial sources.

Potential development of bacterial tolerance to biocides in the industrial environment is examined in this study. Bacteria tolerant to the phenolic-type agent para-chloro-meta-xylenol (PCMX) and the bis-phenol 2,4,4'-trichloro-2'-hydroxydiphenylether (triclosan) were isolated from industrial sources and identified. Minimum inhibitory concentrations (MICs) were determined and compared with those of culture collection (standard) strains. Of around 100 isolates originally obtained, most were naturally tolerant species such as Pseudomonas spp., or showed low tolerance levels. PCMX-tolerant isolates of Pseudomonas stutzeri and triclosan-tolerant isolates of Citrobacter freundii and Acinetobacter johnsonii were retained for further study. Of these, only P. stutzeri and A. johnsonii showed elevated tolerance compared with the standard strains. There was no evidence of tolerance to the other biocide except for Pseudomonas aeruginosa (an intrinsically tolerant microorganism), and tolerances were stable in the absence of selective pressure except for A. johnsonii. Attempts to select or generate increased tolerance in the standard strains were unsuccessful. High tolerances in terms of MIC were not reflected in terms of lethal effects. This study did not produce any evidence suggesting that the presence of residual biocide concentrations in the industrial environment promotes the emergence of bacterial tolerance for them.

Bacteria↗
PubMed2002

A survey of rotational use of biocides in hospital pharmacy aseptic units.

A postal survey of biocide rotation in UK hospital pharmacy aseptic units was carried out. Seventy per cent of respondents stated that biocides were rotated, most frequently in areas outside critical work zones. High-level disinfection was employed when 'aseptic' conditions were required. Decisions on frequency of rotation were most often based on in-house validation or consultation with colleagues. Toxicity and corrosiveness were the criteria rated most important in a rotation policy. Microbiological monitoring was carried out most frequently in critical work zones but less often for handwashing. Most QC hospital pharmacists supported rotation and would prefer a standard period for all applications (monthly). Guidelines need to be clarified to assist staff in decisions regarding biocide rotation.

Anti-Infective Agents, Local↗